The principal objective of this project is to study the mechanisms which bring about the symptoms of cerebral aging and presenile dementia. The research deals with one of the most important health problems in this country - the mentally disabled aged patient. We expect to quantify the age-related neuronal loss in the central cerebral cortex and deep nuclei of humans and animals. Studies will be carried out to determine whether pathological changes similar to those of the senile human brain can be caused by an induced increase of antibrain antibodies in the mouse. Golgi preparations will be used to study the dendritic arbor of neurons with much lipofuscin. We will also study the pathogenesis of axonal and synaptic pathology in aged humans, animals, and experimental models. We also propose to continue the study of brain biopsies which come to us from this and other institutions, and which are done in the course of diagnostic and therapeutic operative procedures. these are from cases with dementia, demyelinating disease, movement disorders, and metabolic disease. The methods of procedure outlined in the grant proposal include automated counting and measuring of glia and nerve cells by image analysis apparatus, light and electron microscopic studies, and biochemical and immunological methodology. BIBLIOGRAPHIC REFERENCES: Powers, James M.; Balentine, J. Douglas; Wisniewski, Henryk M.; and Terry, Robert D.: Retroperitoneal Ganglioneuroblastoma: A Kaleidoscope of Neuronal Degeneration. A Light and Electron Microscopic Study. Journal of Neuropathology and Experimental Neurology; 35: 14 - 25, 1976. Powers, James M.; and Wisniewski, Henryk; and Terry, Robert D.: Lack of Amyloidosis and Renal Disease in A Strain Mice. A.M.A., Archives of Pathology and Laboratory Medicine; 100: 69 - 73, 1976.